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Int. J. Mol. Sci. 2016, 17(9), 1443; doi:10.3390/ijms17091443

The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

1
Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania
2
Institute of Biochemistry, Ernst-Moritz-Arndt-University, Felix-Hausdorff Street 4, Greifswald 17487, Germany
3
Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania
4
MedFuture Research Center for Advanced Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 4-6, Gh. Marinescu Street 23, Cluj-Napoca 400349, Romania
*
Author to whom correspondence should be addressed.
Academic Editors: Antonio Segura-Carretero and Ana Maria Gómez Caravaca
Received: 18 April 2016 / Revised: 22 August 2016 / Accepted: 23 August 2016 / Published: 31 August 2016
(This article belongs to the Special Issue Advances in Molecular Research of Functional and Nutraceutical Food)
View Full-Text   |   Download PDF [4027 KB, uploaded 31 August 2016]   |  

Abstract

Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention. View Full-Text
Keywords: soy isoflavones; breast cancer; metabolomics; MTT assay; 1H-NMR; GC-MS; glucose uptake; glutamine uptake soy isoflavones; breast cancer; metabolomics; MTT assay; 1H-NMR; GC-MS; glucose uptake; glutamine uptake
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Uifălean, A.; Schneider, S.; Gierok, P.; Ionescu, C.; Iuga, C.A.; Lalk, M. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach. Int. J. Mol. Sci. 2016, 17, 1443.

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